Catharina C.M. Schuiling-Veninga

Trends and patterns of antidepressant use in children and adolescents from five western countries, 2005-2012

Following the FDA black box warning in 2004, substantial reductions in antidepressant (ATD) use were observed within 2 years in children and adolescents in several countries. However, whether these reductions were sustained is not known. The objective of this study was to assess more recent trends in ATD use in youth (0-19 years) for the calendar years 2005/6-2012 using data extracted from regional or national databases of Denmark, Germany, the Netherlands, the United Kingdom (UK), and the United States (US). In a repeated cross-sectional design, the annual prevalence of ATD use was calculated and stratified by age, sex, and according to subclass and specific drug. Across the years, the prevalence of ATD use increased from 1.3% to 1.6% in the US data (+26.1%); 0.7% to 1.1% in the UK data (+54.4%); 0.6% to 1.0% in Denmark data (+60.5%); 0.5% to 0.6% in the Netherlands data (+17.6%); and 0.3% to 0.5% in Germany data (+49.2%). The relative growth was greatest for 15-19 year olds in Denmark, Germany and UK cohorts, and for 10-14 year olds in Netherlands and US cohorts. While SSRIs were the most commonly used ATDs, particularly in Denmark (81.8% of all ATDs), Germany and the UK still displayed notable proportions of tricyclic antidepressant use (23.0% and 19.5%, respectively). Despite the sudden decline in ATD use in the wake of government warnings, this trend did not persist, and by contrast, in recent years, ATD use in children and adolescents has increased substantially in youth cohorts from five Western countries.

Prenatal exposure to acid-suppressive drugs and the risk of allergic diseases in the offspring: a cohort study

Recent studies reported increased risks for the development of asthma in children after prenatal exposure to acid‐suppressive drugs. As a result of common pathogenesis, associations could also be present for other allergic diseases.

International trends in clozapine use: a study in 17 countries

There is some evidence that clozapine is significantly underutilised. Also, clozapine use is thought to vary by country, but so far no international study has assessed trends in clozapine prescribing. Therefore, this study aimed to assess clozapine use trends on an international scale, using standardised criteria for data analysis.

Antibiotic use during pregnancy and asthma in preschool children: the influence of confounding.

A recent study suggested that early‐life intestinal microbiota may play an important role in the development of childhood asthma, indicating that antibiotics taken during early life or in late pregnancy may be associated with childhood asthma.

International trends in antipsychotic use : A study in 16 countries, 2005-2014

The objective of this study was to assess international trends in antipsychotic use, using a standardised methodology. A repeated cross-sectional design was applied to data extracts from the years 2005 to 2014 from 16 countries worldwide. During the study period, the overall prevalence of antipsychotic use increased in 10 of the 16 studied countries. In 2014, the overall prevalence of antipsychotic use was highest in Taiwan (78.2/1000 persons), and lowest in Colombia (3.2/1000). In children and adolescents (0-19 years), antipsychotic use ranged from 0.5/1000 (Lithuania) to 30.8/1000 (Taiwan). In adults (20-64 years), the range was 2.8/1000 (Colombia) to 78.9/1000 (publicly insured US population), and in older adults (65+ years), antipsychotic use ranged from 19.0/1000 (Colombia) to 149.0/1000 (Taiwan). Atypical antipsychotic use increased in all populations (range of atypical/typical ratio: 0.7 (Taiwan) to 6.1 (New Zealand, Australia)). Quetiapine, risperidone, and olanzapine were most frequently prescribed. Prevalence and patterns of antipsychotic use varied markedly between countries. In the majority of populations, antipsychotic utilisation and especially the use of atypical antipsychotics increased over time. The high rates of antipsychotic prescriptions in older adults and in youths in some countries merit further investigation and systematic pharmacoepidemiologic monitoring.

Trends in ADHD medication use in children and adolescents in five western countries, 2005-2012

Over the last two decades, the use of ADHD medication in US youth has markedly increased. However, less is known about ADHD medication use among European children and adolescents. A repeated cross-sectional design was applied to national or regional data extracts from Denmark, Germany, the Netherlands, the United Kingdom (UK) and the United States (US) for calendar years 2005/2006-2012. The prevalence of ADHD medication use was assessed, stratified by age and sex. Furthermore, the most commonly prescribed ADHD medications were assessed. ADHD medication use prevalence increased from 1.8% to 3.9% in the Netherlands cohort (relative increase: +111.9%), from 3.3% to 3.7% in the US cohort (+10.7%), from 1.3% to 2.2% in the German cohort (+62.4%), from 0.4% to 1.5% in the Danish cohort (+302.7%), and from 0.3% to 0.5% in the UK cohort (+56.6%). ADHD medication use was highest in 10-14-year olds, peaking in the Netherlands (7.1%) and the US (8.8%). Methylphenidate use predominated in Europe, whereas in the US amphetamines were nearly as common as methylphenidate. Although there was a substantially greater use of ADHD medications in the US cohort, there was a relatively greater increase in ADHD medication use in youth in the four European countries. ADHD medication use patterns in the US differed markedly from those in western European countries.

Off-Label Prescriptions of Low-Dose Quetiapine and Mirtazapine for Insomnia in The Netherlands

To the Editors: H ypnotics, such as benzodiazepines, are widely used to treat insomnia but have serious disadvantages, such as hangover effects on the next day, rapid development of tolerance, rebound insomnia upon drug discontinuation, and a high risk of misuse and abuse. Therefore, they should be used only for short time intervals. In The Netherlands, since 2009, benzodiazepines for the treatment of insomnia are no longer reimbursed in an attempt to reduce their use and lower health care costs. If prescribed, patients have to cover the cost of the medicines themselves. Possibly in search of an alternative, the prescription rate of low doses of other psychotropic medication with sedative effects seems to increase. In particular, quetiapine and mirtazapine are used “off-label” (OL), thus without regulatory approval, to treat sleep difficulties, but little is known about prescribing patterns. For quetiapine, an antipsychotic drug on the market since 1997, the recommended dose range for the licensed indications is 150 to 800 mg/d. Yet, 54% of the total quetiapine prescriptions in 2010 in England were for the 25 mg tablet. There are only limited data supporting the use of low doses of quetiapine in patients suffering from insomnia. One study in healthy volunteers and 2 in patients with insomnia found shortened sleep latency and increased total sleep time. Mirtazapine, on the market since 1994, is used to treat depression in a recommended dose range between 30 and 45 mg/d. In clinical practice, doses of 15 mg or less are used to improve sleep. Of the prescriptions for insomnia in the United States, 45% concerned OL antidepressants, frequently mirtazapine. Studies of mirtazapine in doses between 15 and 60 mg in insomniacs showed increased total sleep time and improved sleep efficiency. Adverse effects of the chronic use of low doses of quetiapine and mirtazapine have been reported, although this has not been thoroughly investigated. Both drugs have been associated with daytime sleepiness and weight gain in clinical studies. Case reports describe restless legs syndrome, akathisia, and hepatotoxicity for low-dose quetiapine and

Adherence to hypertension medication : Quantitative and qualitative investigations in a rural Northern Vietnamese community

Objectives The purposes of this study were to assess the adherence to medication of hypertensive patients visiting community health stations in a rural area in Vietnam, to examine the relationship between levels of adherence and cardiovascular risk among hypertensive patients and to further understand factors influencing adherence. Methods This study is part of a prospective one-year study conducted on hypertension management in a population aged 35 to 64 years. Data on age, sex, blood pressure and blood test results were collected at baseline. Cardiovascular risk was based on the Cardiovascular Risk Prediction Model for populations in Asia. To calculate medication adherence, the number of days the drug was taken was divided by the number of days since the first day of the prescription. A threshold of 80% was applied to differentiate between adherence and non-adherence. In-depth interviews were conducted among 18 subjects, including subjects classified as adherent and as non-adherent. Results Among 315 patients analyzed, 49.8% of the patients were adherent. Qualitative investigation revealed discrepancies in classification of adherence and non-adherence based on quantitative analysis and interviews. No significant difference in medication compliance between two cardiovascular disease risk groups (<10% vs. >10% risk) was found, also not after controlling for age, sex, and ethnicity (adjusted odds ratio at 1.068; 95% CI: 0.614 to 1.857). The odds of medication adherence in females was 1.531 times higher than in males but the difference was not statistically significant (95% CI: 0.957 to 2.448). Each one-year increase in age resulted in patients being 1.036 times more likely to be compliant (95% CI: 1.002 to 1.072). Awareness of complications related to hypertension was given as the main reason for adherence to therapy. Conclusions Medication adherence rate was relatively low among hypertensive subjects. The data suggest that rather than risk profile, the factor of age should be considered for guiding the choice on who to target for improving medication adherence.

Impact of Muscarinic M3 Receptor Antagonism on the Risk of Type 2 Diabetes in Antidepressant-Treated Patients: A Case-Controlled Study

BackgroundM3 muscarinic receptor antagonism has been associated with glucose intolerance and disturbance of insulin secretion.ObjectiveOur objective was to examine the risk of type 2 diabetes mellitus (T2DM) in patients using antidepressants with and without M3 muscarinic receptor antagonism (AD_antaM3 and AD_nonantaM3, respectively).MethodsWe designed a case–control study using a pharmacy prescription database. We selected a cohort of patients who initiated antidepressant use between the ages of 20 and 40 years and who did not receive any anti-diabetic prescriptions at baseline. Cases were defined as those who developed T2DM [i.e., receiving oral anti-diabetic medication, Anatomical Therapeutic Chemical (ATC) code A10B] during the follow-up period (1994–2014), and ten random controls were picked for each case from the cohort of patients who did not develop T2DM.ResultsA total of 530 cases with incident T2DM and 5300 controls were included. Compared with no use of antidepressants during the previous 2 years, recent (within the last 6 months) exposure to AD_antaM3 was associated with a moderately increased risk of T2DM: adjusted odds ratio 1.55 (95% confidence interval 1.18–2.02). In the stratified analyses, this association was dose dependent (>365 defined daily doses) and significant for patients who were in the younger age group (<45 years at the end of follow-up), were female and had no co-morbidity. On the other hand, recent exposure to AD_nonantaM3 was not associated with a risk for T2DM in any of our analyses.ConclusionOur results suggest that exposure to AD_antaM3 was associated with the development of T2DM among antidepressant users.

Models to Predict the Burden of Cardiovascular Disease Risk in a Rural Mountainous Region of Vietnam

OBJECTIVE To compare and identify the most appropriate model to predict cardiovascular disease (CVD) in a rural area in Northern Vietnam, using data on hypertension from the communities. METHODS A cross-sectional survey was conducted including all residents in selected communities, aged 34 to 65 years, during April to August 2012 in Thai Nguyen province. Data on age, sex, smoking status, blood pressure, and blood tests (glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol) were collected to identify the prevalence of high blood pressure and to use as input variables for the models. We compared three models, Asian, Chinese Multiple-provincial Cohort Study (CMCS), and Framingham, to estimate cardiovascular risk in the coming years in this context and compare these models and outcomes. RESULTS The prevalence of high blood pressure in these communities was lower than reported nationally (12.3%). CVD risk differed greatly depending on the model applied: approximately 21% of the subjects according to the CMCS and Asian models, but 37% using the Framingham model, had more than 10% risk for CVD. In the group without current CVD, these numbers decreased to 9% using the CMCS and Asian models but increased to 28% according to the Framingham model. There were no significant differences between the Asian and CMCS models, but differences were highly significant when comparing Asian versus Framingham or CMCS versus Framingham model. CONCLUSIONS The Asian and CMCS models provided similar results in predicting CVD risk in the Vietnamese population in Thai Nguyen. The Framingham model provided vastly different results. The suggestion may be that for the specific Vietnamese setting, the Asian and CMCS models provide most valid and reliable results; however, this has to be investigated in further analyses using real-life data for potential confirmation.